Vaccination with DNA plasmids expressing Gn coupled to C3d or alphavirus replicons expressing Gn protects mice against rift valley fever virus

Background: Rift Valley fever (RVF) is an arthropod-borne viral zoonosis. Rift Valley fever virus (RVFV) is an important biological threat with the potential to spread to new susceptible areas. In addition, it is a potential biowarfare agent. Methodology/Principal Findings: We developed two potential vaccines, DNA plasmids and alphavirus replicons, expressing the Gn glycoprotein of RVFV alone or fused to three copies of complement protein, C3d. Each vaccine was administered to mice in an all DNA, all replicon, or a DNA prime/replicon boost strategy and both the humoral and cellular responses were assessed. DNA plasmids expressing Gn-C3d and alphavirus replicons expressing Gn elicited high titer neutralizing antibodies that were similar to titers elicited by the live-attenuated MP12 virus. Mice vaccinated with an inactivated form of MP12 did elicit high titer antibodies, but these antibodies were unable to neutralize RVFV infection. However, only vaccine strategies incorporating alphavirus replicons elicited cellular responses to Gn. Both vaccines strategies completely prevented weight loss and morbidity and protected against lethal RVFV challenge. Passive transfer of antisera from vaccinated mice into naïve mice showed that both DNA plasmids expressing Gn-C3d and alphavirus replicons expressing Gn elicited antibodies that protected mice as well as sera from mice immunized with MP12. Conclusion/Significance: These results show that both DNA plasmids expressing Gn-C3d and alphavirus replicons expressing Gn administered alone or in a DNA prime/replicon boost strategy are effective RVFV vaccines. These vaccine strategies provide safer alternatives to using live-attenuated RVFV vaccines for human use. © 2010 Bhardwaj et al

Sagittal realignment osteotomy for increased posterior tibial slope after opening-wedge high tibial osteotomy: a case report

A 40 year old welder who underwent opening-wedge high tibial osteotomy for correction of alignment in a varus knee developed persistent pain with loss of knee extension. The posterior tibial slope increased from 9 degrees to 20 degrees after the osteotomy and caused the anteromedial knee pain and limited extension. The patient then underwent a revision osteotomy using a closing wedge technique to correct tibial slope. The osteotomy was performed, first from the medial cortex in the lateral direction, and second in the anteroposterior direction to remove the tibial bone in wedge shape and obtain full extension of the knee. The posterior tibial slope decreased to 8 degrees after the revision osteotomy and the patients returned to pain-free daily life. We reviewed this unique technique for correction of sagittal malalignment using a closing-wedge osteotomy for revision after opening-wedge osteotomy

Hemangiopericytoma in the sacrococcygeal space: a case report

<p>Abstract</p> <p>Introduction</p> <p>A hemangiopericytoma is a rare, soft-tissue tumor of vascular origin derived from a pericyte of Zimmerman, which is a modified smooth muscle cell that surrounds the small blood vessels. Hemangiopericytomas can occur wherever there are vascular capillaries. However, there are no previous reports of a hemangiopericytoma in the sacrococcygeal space.</p> <p>Case presentation</p> <p>We describe the first reported case of a hemangiopericytoma found in the sacrococcygeal space. A 47-year-old Japanese woman presented with a palpable tumor on the left side of her anus. Preoperative imaging indicated that the tumor was in the sacrococcygeal space without invasion of other organs. A complete resection was performed via a parasacral incision. The histological and immunohistochemical staining patterns supported the diagnosis of a hemangiopericytoma.</p> <p>Conclusion</p> <p>A complete resection without piecemeal excision is the best way to treat a hemangiopericytoma. Recognizing the presence of a hemangiopericytoma in the sacrococcygeal space requires appropriate surgery.</p

Comparative genomics of prevaccination and modern Bordetella pertussis strains

Contains fulltext : 89571.pdf (publisher's version ) (Open Access)BACKGROUND: Despite vaccination since the 1950s, pertussis has persisted and resurged. It remains a major cause of infant death worldwide and is the most prevalent vaccine-preventable disease in developed countries. The resurgence of pertussis has been associated with the expansion of Bordetella pertussis strains with a novel allele for the pertussis toxin (Ptx) promoter, ptxP3, which have replaced resident ptxP1 strains. Compared to ptxP1 strains, ptxP3 produce more Ptx resulting in increased virulence and immune suppression. To elucidate how B. pertussis has adapted to vaccination, we compared genome sequences of two ptxP3 strains with four strains isolated before and after the introduction vaccination. RESULTS: The distribution of SNPs in regions involved in transcription and translation suggested that changes in gene regulation play an important role in adaptation. No evidence was found for acquisition of novel genes. Modern strains differed significantly from prevaccination strains, both phylogenetically and with respect to particular alleles. The ptxP3 strains were found to have diverged recently from modern ptxP1 strains. Differences between ptxP3 and modern ptxP1 strains included SNPs in a number of pathogenicity-associated genes. Further, both gene inactivation and reactivation was observed in ptxP3 strains relative to modern ptxP1 strains. CONCLUSIONS: Our work suggests that B. pertussis adapted by successive accumulation of SNPs and by gene (in)activation. In particular changes in gene regulation may have played a role in adaptation

Role of high tibial osteotomy in chronic injuries of posterior cruciate ligament and posterolateral corner

High tibial osteotomy (HTO) is a surgical procedure used to change the mechanical weight-bearing axis and alter the loads carried through the knee. Conventional indications for HTO are medial compartment osteoarthritis and varus malalignment of the knee causing pain and dysfunction. Traditionally, knee instability associated with varus thrust has been considered a contraindication. However, today the indications include patients with chronic ligament deficiencies and malalignment, because an HTO procedure can change not only the coronal but also the sagittal plane of the knee. The sagittal plane has generally been ignored in HTO literature, but its modification has a significant impact on biomechanics and joint stability. Indeed, decreased posterior tibial slope causes posterior tibia translation and helps the anterior cruciate ligament (ACL)-deficient knee. Vice versa, increased tibial slope causes anterior tibia translation and helps the posterior cruciate ligament (PCL)-deficient knee. A review of literature shows that soft tissue procedures alone are often unsatisfactory for chronic posterior instability if alignment is not corrected. Since limb alignment is the most important factor to consider in lower limb reconstructive surgery, diagnosis and treatment of limb malalignment should not be ignored in management of chronic ligamentous instabilities. This paper reviews the effects of chronic posterior instability and tibial slope alteration on knee and soft tissues, in addition to planning and surgical technique for chronic posterior and posterolateral instability with HTO

Four-electron deoxygenative reductive coupling of carbon monoxide at a single metal site

Carbon dioxide is the ultimate source of the fossil fuels that are both central to modern life and problematic: their use increases atmospheric levels of greenhouse gases, and their availability is geopolitically constrained. Using carbon dioxide as a feedstock to produce synthetic fuels might, in principle, alleviate these concerns. Although many homogeneous and heterogeneous catalysts convert carbon dioxide to carbon monoxide, further deoxygenative coupling of carbon monoxide to generate useful multicarbon products is challenging. Molybdenum and vanadium nitrogenases are capable of converting carbon monoxide into hydrocarbons under mild conditions, using discrete electron and proton sources. Electrocatalytic reduction of carbon monoxide on copper catalysts also uses a combination of electrons and protons, while the industrial Fischer–Tropsch process uses dihydrogen as a combined source of electrons and electrophiles for carbon monoxide coupling at high temperatures and pressures6. However, these enzymatic and heterogeneous systems are difficult to probe mechanistically. Molecular catalysts have been studied extensively to investigate the elementary steps by which carbon monoxide is deoxygenated and coupled, but a single metal site that can efficiently induce the required scission of carbon–oxygen bonds and generate carbon–carbon bonds has not yet been documented. Here we describe a molybdenum compound, supported by a terphenyl–diphosphine ligand, that activates and cleaves the strong carbon–oxygen bond of carbon monoxide, enacts carbon–carbon coupling, and spontaneously dissociates the resulting fragment. This complex four-electron transformation is enabled by the terphenyl–diphosphine ligand, which acts as an electron reservoir and exhibits the coordinative flexibility needed to stabilize the different intermediates involved in the overall reaction sequence. We anticipate that these design elements might help in the development of efficient catalysts for converting carbon monoxide to chemical fuels, and should prove useful in the broader context of performing complex multi-electron transformations at a single metal site

Visual motion with pink noise induces predation behaviour

Visual motion cues are one of the most important factors for eliciting animal behaviour, including predator-prey interactions in aquatic environments. To understand the elements of motion that cause such selective predation behaviour, we used a virtual plankton system where the predation behaviour in response to computer-generated prey was analysed. First, we performed motion analysis of zooplankton (Daphnia magna) to extract mathematical functions for biologically relevant motions of prey. Next, virtual prey models were programmed on a computer and presented to medaka (Oryzias latipes), which served as predatory fish. Medaka exhibited predation behaviour against several characteristic virtual plankton movements, particularly against a swimming pattern that could be characterised as pink noise motion. Analysing prey-predator interactions via pink noise motion will be an interesting research field in the future

Microleakage and Resin-to-Dentin Interface Morphology of Pre-Etching versus Self-Etching Adhesive Systems

The purpose of this study was to compare the microleakage and tissue-adhesive interface morphology from Class V restorations using different systems of dentin adhesives. Class V cavities were prepared on buccal surfaces of 27 extracted caries-free molars and premolars. Teeth were randomly assigned to one of three groups: (1) Prime & Bond NT, a 5th generation system using an initial step of total etch followed by a second step of application of a self bonding primer (2) Clearfil SE Bond, a 5th generation adhesive system employing two separate steps of self-etch priming and subsequent bonding (3) One-up Bond F, a 6th generation one step self-etching, self-priming and self-bonding adhesive. Microleakage and interface morphology of teeth restored with these adhesives and a composite resin were evaluated. Kruskal-Wallis Test (p = 0.05) was used to analyze the results. SEM analysis was used to relate interface morphology to microleakage. The mean and (SD) values of microleakage were: Prime and Bond NT: 0.15 (0.33), Clearfil SE Bond: 0.06 (0.17) and One-up Bond F: 2.96 (0.63). The mean microleakage for One-up Bond was significantly higher than for the other groups (p<0.05). Protruding tags in dentin channels were observed in Prime and Bond and Clearfil systems, but not in One-up Bond. The single step adhesive system, although more convenient for the clinician, uses a low viscosity formulation difficult to keep in place on cavity walls. It also tends to be too aggressive and hydrophilic to create an impermeable hybridized tissue-adhesive interfacial layer resistant to microleakage. Two-step adhesive systems, on the other hand, were retained on all segments of the cavosurface during application, and formed a hybridized interfacial layer resistant to microleakage

Anatomic and histological study of the anterolateral aspect of the knee: a SANTI Group investigation

Background: The structure and function of the anterolateral aspect of the knee have been significantly debated, with renewed interest in this topic since the description of the anterolateral ligament (ALL). Purpose: To define and describe the distinct structures of the lateral knee and to correlate the macroscopic and histologic anatomic features. Study Design: Descriptive laboratory study. Methods: Twelve fresh-frozen human cadavers were used for anatomic analysis. In the left knee, a layer-by-layer dissection and macroscopic analysis were performed. In the right knee, an en bloc specimen was obtained encompassing an area from the Gerdy tubercle to the posterior fibular head and extending proximally from the anterior aspect to the posterior aspect of the lateral femoral epicondyle. The en bloc resection was then frozen, sliced at the level of the joint line, and reviewed by a musculoskeletal pathologist. Results: Macroscopically, the lateral knee has 4 main layers overlying the capsule of the knee: the aponeurotic layer, the superficial layer including the iliotibial band (ITB), the deep fascial layer, and the ALL. Histologically, 8 of 12 specimens demonstrated 4 consistent, distinct structures: the ITB, the ALL, the lateral collateral ligament, and the meniscus. Conclusion: The lateral knee has a complex orientation of layers and fibers. The ALL is a distinct structure from the ITB and is synonymous to the previously described capsulo-osseous layer of the ITB. Clinical Relevance: Increasingly, lateral extra-articular procedures are performed at the time of anterior cruciate ligament reconstruction. Understanding the anatomic features of the anterolateral aspect of the knee is necessary to understand the biomechanics and function of the structures present and allows surgeons to attempt to replicate those anatomic characteristics when performing extra-articular reconstruction

Network Analysis of Differential Expression for the Identification of Disease-Causing Genes

Genetic studies (in particular linkage and association studies) identify chromosomal regions involved in a disease or phenotype of interest, but those regions often contain many candidate genes, only a few of which can be followed-up for biological validation. Recently, computational methods to identify (prioritize) the most promising candidates within a region have been proposed, but they are usually not applicable to cases where little is known about the phenotype (no or few confirmed disease genes, fragmentary understanding of the biological cascades involved). We seek to overcome this limitation by replacing knowledge about the biological process by experimental data on differential gene expression between affected and healthy individuals. Considering the problem from the perspective of a gene/protein network, we assess a candidate gene by considering the level of differential expression in its neighborhood under the assumption that strong candidates will tend to be surrounded by differentially expressed neighbors. We define a notion of soft neighborhood where each gene is given a contributing weight, which decreases with the distance from the candidate gene on the protein network. To account for multiple paths between genes, we define the distance using the Laplacian exponential diffusion kernel. We score candidates by aggregating the differential expression of neighbors weighted as a function of distance. Through a randomization procedure, we rank candidates by p-values. We illustrate our approach on four monogenic diseases and successfully prioritize the known disease causing genes